Biotechnologically-produced cellulose-containing article for dermatological use

ABSTRACT

A cellulose-containing article for treating an area of skin, wherein the article comprises BNC in an amount of at least 1% by weight and at most 15% by weight, comprises fluid in an amount of at least 85% by weight and at most 99% by weight, has an average thickness of at least 0.5 mm and at most 8 mm, wherein the BNC is of microbial origin.

FIELD OF THE INVENTION

The present invention relates to a biotechnologically producednano-structured cellulose (BNC)-containing article for treating an areaof skin, medical and non-medical methods for the treatment of an area ofa subject's skin, and methods of manufacturing said BNC-containingarticle.

BACKGROUND OF THE INVENTION

It is known in the art that application of pure water provides anexcellent possibility to relax and clean skin. However, there is a needto apply a water reservoir, which can interact with the skin and providemoisture to the skin for a prolonged time period and without the need ofimmersing or bathing the skin. For this purpose cellulose articles areknown, which can be applied in order to provide such water reservoir tothe skin.

Particularly, bacterial cellulose materials have been used in medicaland cosmetic applications in the prior art. This material is anextracellular polysaccharide produced by different bacteria, includingKomatagaibacter, Agrobacter and Sarcina strains (I. F. Almeida et al.,Bacterial cellulose membranes as drug delivery systems: An in vivo skincompatibility study, Eur. J. Pharm. Biopharm. (2014)).

Methods for producing bacterial-cellulose are known in the art.Particularly, static or discontinuous production processes, like staticfermentation, are used. Particularly, bacterial BNC produced by staticor discontinuous production processes is known, however, relativelyexpensive, and comes along with various drawbacks, particularly withdis-advantageous or at least sub-optimal properties of the producedbacterial cellulose. Moreover, in static manufacturing processes theproduction of bacterial BNC is limited by the batch-wise production. Thebacterial cellulose produced in such processes is of relatively heavyweight and possesses a disadvantageously low tensile strength. Arespective article for application to skin, moreover, needs anadditional support or other fixation means. Therefore, such articlesusually do not allow a subject moving unimpededly while the articleremains on the area of skin. Due to the relatively low tensile strength,the articles of the prior art also easily tear. Moreover, many articlesknown in the art do not provide a sufficient moisturizing effect withoutwet feeling and a soft and smooth surface feel at the same time.

In Almeida et al. the authors tested skin compatibility of bacterialcellulose patches by applying the patches to the subject's forearms for24 hours. The patches contained 5% of water and were fixed to the skinusing aluminum chambers. One patch contained 32% of glycerin. Theglycerin containing patch showed improved bendability.

The document DE 10 2004 002 990 A1 describes a nano-structured materialthat can be used as a cosmetic pad or wound dressing. It may be used toachieve a cooling effect by evaporation of liquid contained in thematerial. However, the nano-structured material is rather thin. Ifthicker material is used, the material needs a supporting structure forreinforcement. In other embodiments, the material is used together withan adhesive or sewn to the skin. However, this document does notdisclose an article capable of adhering to the skin without any fixationmeans or means to support the article's structural integrity. Additionalsupport or fixation means destroy the soft and smooth surface feel ofbacterial cellulose films.

The document FR 2 916 971 A1 discloses a slimming composition forapplication on the thighs including a bacterial cellulose substrate. Thesubstrate includes at least 10% by weight of bacterial cellulose and anactive substance. However, even at a very low thickness of only 1 mm,the article does not adhere to the skin without auxiliary measures.Particularly, the substrate should be used together with a supportmaterial so that it stays on the skin after application.

The document US 2011/0286948 A1 discloses a bacterial cellulose filmthat has a density gradient, wherein—when applied to the skin—the partof the film that is in contact with the skin surface has a lower densityof microbial fibers than the side facing away from the skin surface.However, the bacterial cellulose film is produced using staticfermentation.

The document WO 2007/091801 A1 discloses a bacterial cellulose sheet foruse on the burned or otherwise wounded skin. The sheet has absorptiveproperties towards exudates. The sheet can be soaked with a solution ofan active ingredient to obtain a sheet having from 0.5 to 10 mmthickness. The production process uses fruit juice as the cultivationmedium. However, the production process is discontinuous and themoisture content of the finished product is very low.

The document US 2013/0244977 A1 teaches a bio-cellulose-containing maskthat is produced in a cultivation medium containing ginseng extracts.The sheet is dried after preparation and then impregnated with acosmetic emulsion. However, the bacterial cellulose is produced in astatic process.

The document US 2009/0041815 A1 relates to a cosmetic compositioncomprising bacterial cellulose and a powder. A method is described inwhich the bacterial cellulose is brought into contact with the powderand afterwards applied to the skin. However, a support is needed foradhesion of the substrate to the skin. Moreover, the bacterial celluloseis produced using rotating disc fermentation. Such rotating discfermentation, however, leads to bacterial cellulose having a tensilestrength of even less than the bacterial cellulose produced usingstationary conditions. The desired advantageous properties according tothe present invention, however, are not met.

The document WO 2013/094077 A1 discloses a cosmetic sheet for lipscomprising bacterial cellulose, water and at least one non-volatile oil.The sheet is supposed to remain on the lips for 10 seconds to 20minutes. It is an object of the invention disclosed in that documentthat the sheet should adhere to the lips. However, treatment time isvery short. Moreover, the bacterial cellulose is produced using a staticproduction process, which makes production of the product veryexpensive, and comes along with further disadvantageous properties ofthe produced cellulose. It is mentioned that adhesive power of the sheetis sufficient because it contains water. However, this is only true ifthe thickness of the cosmetic sheet is low and the desired adhesion timeis short. It is not disclosed in this document how much water orbacterial cellulose is used in the cosmetic sheet.

The document WO 2012/131623 A2 discloses a fractional cosmetic treatmentusing a laser and micro needles. It has to be acknowledged that suchlaser fracturing is a relatively specific treatment and is related torelatively specific needs. The fractional treatment is applied in orderto reduce the barrier function of the skin. After fractional treatmentan aqueous material is applied. However, the bacterial cellulose isproduced in a static process and the use of a support, e.g. a textilewrap, is suggested.

Facial dermatitis, particularly perioral, periorbital, periocular orperinasal dermatitis, is a skin disease characterized by multiple smallpapules, pustules and vesicles which are localized to the perioral skinaround the mouth, perinasal or nasolabial folds around the nostrils, orperiocular area around the eyes, respectively. It most commonly affectswomen between the ages of 20 and 45 years, but may also affect children,men and the elderly. It is common, and has a tendency to recur inindividuals who have had it once. Facial dermatitis may be asymptomatic,or may be associated with a burning, stinging sensation in the affectedareas. The exact cause of the disease remains unknown. Followingover-treatment, the skin is no longer able to produce the necessary fatsand lipids, so that it is dry and scaly. The often considerably impairedappearance causes that the affected areas are more intensively treatedand cared, and particularly moisturized, whereupon the rash becomesaggravated. Subjects suffering from facial dermatitis usually alsoincreasingly apply cosmetics and skin-care products and, particularly,ointments and crèmes comprising cortisone. These cortisone productsinitially may achieve an improvement, but this is only short-lived. Itis known in the art that the rash, despite further treatment withcortisone, is boosted and intensifies. For an effective treatment, thecauses mentioned must be eliminated. In particular, the regular use ofcosmetic creams (“moisturizers”) should be avoided. In addition,phototherapy may be applied. During therapy, the affected skin areas mayonly be cleaned with water. For such treatment, particularly theabove-described bio-cellular cellulose articles may be used, whichhowever show the mentioned draw-backs.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide an article and amedical, cosmetic or esthetic method which overcomes the above-describeddrawbacks.

It is a further object of the present invention to provide an articleand a medical, cosmetic or esthetic method, wherein a subject's skin isprovided with a soothing, cooling, caring, and alleviative effect to anarea of skin by applying the article to the skin. It is a still furtherobject of the present invention to provide an article and a medical,cosmetical or esthetical method, wherein the subject is able to moveunimpededly while the article remains on the area of skin, wherein thearticle provides a moisturizing effect without wet feeling, wherein thearticle is lightweight and has very soft and smooth surface feel,wherein the article has an alleviating effect on skin that suffers fromburns and/or all forms of dermatitis. Particularly, the article shouldbe biodegradable and be produced by a very economical method.

It is a particular object of the present invention to provide an articleand a medical, cosmetic or esthetic method useful in the medicaltreatment, or in the cosmetical or esthetical treatment, respectively,of skin diseases and skin conditions.

These and other problems are solved by the subject matter of theattached independent claims.

The above-described objects of the invention are achieved by an articlecontaining biotechnologically produced nano-structured cellulose (BNC)for treating an area of skin, wherein the article comprises BNC in anamount of at least 1% by weight and at most 15% by weight, comprisesfluid in an amount of at least 85% by weight and at most 99% by weight,has an average thickness of at least 0.5 mm and at most 8 mm, whereinthe BNC is of a microbial origin and wherein the article has apolydispersity index of less than 30; or a method for treatment of anarea of a subject's skin, comprising a. applying a cellulose-containingarticle to said area of skin, b. leaving the article on the skin forpredetermined time period, c. removing the article from the skin,wherein the article comprises biotechnologically produced nanostructuredcellulose (BNC)in an amount of at least 1% by weight and at most 15% byweight, comprises fluid in an amount of at least 85% by weight and atmost 99% by weight, has an average thickness of at least 0.5 mm and atmost 8 mm, and wherein the BNC is of microbial origin and the articlehas a polydispersity index of less than 3.0.

In a first aspect, the present invention provides a BNC-containingarticle for treating an area of skin according to the present invention,which comprises BNC in an amount of at least 1% by weight and at most15% by weight, fluid in an amount of at least 85% by weight and at most99% by weight, and which has an average thickness of at least 0.5 mm andat most 8 mm. The BNC contained in said article is of microbial origin.

In an embodiment, the present invention preferably provides aBNC-containing article for treating an area of skin according to thepresent invention, which consists of BNC in an amount of at least 1% byweight and at most 15% by weight, fluid in an amount of at least 85% byweight and at most 99% by weight, and which has an average thickness ofat least 0.5 mm and at most 8 mm.

In a further aspect, the present invention provides a method fortreatment of an area of a subject's skin. Said method comprises at leastthe steps of

a. applying a BNC-containing article according to the present inventionto said area of skin,

b. leaving the article on the skin for a predetermined time period,

c. removing the article from the skin.

The article of the present invention is particularly suitable for theuse in the method of treatment according to the present invention. Thevarious features, embodiments and advantages described in connectionwith the article may thus be also features, embodiments and advantagesof the method, and vice versa.

The present invention considers particularly the application of thearticle in the treatment of various skin conditions, disorders ordiseases: Particularly, said skin conditions, disorders or diseases maybe selected from the group comprising dermatitis, particularly facialdermatitis, more particularly perioral, periorbital, periocular orperinasal dermatitis; dry skin; atopic dermatitis; burns; psoriasis;acne; rosacea and/or skin that has undergone photodynamic therapy.Thereby, the present inventive article and method is particularly usefulin the treatment of dermatitis, particularly facial dermatitis, moreparticularly perioral, periorbital, periocular or perinasal dermatitis;dry skin; atopic dermatitis; burns; psoriasis; acne; rosacea and/or skinthat has undergone photodynamic therapy. Particularly the treatment ofdermatitis, particularly facial dermatitis, more particularly perioral,periorbital, periocular or perinasal dermatitis is considered herein.

The term “skin” in the sense of the present invention comprises theactual skin (comprising epidermis and dermis) as the outer covering ofthe body and additionally comprises mucous membranes, in particularnasal mucosa and/or oral mucosa. According to preferred embodiments ofthe present invention, the inventive article is applied subsequent toplastic surgery. In such embodiments, the article may support healing ofthe skin, in particular of the mucous membrane. In particularlypreferred embodiments, the article is applied in rolled form, especiallyin form of a tamponade, particularly in form of a nasal tamponade.

The treatment according to the present invention may be a non-medicaltreatment, particularly a cosmetic or esthetic treatment; or a medicaltreatment.

Depending on the intended purpose, the article may comprise or may notcomprise at least one active agent, particularly a pharmaceuticallyactive agent and/or a naturally active agent and/or a cosmeticallyactive agent and/or an esthetically active agent. In some embodiments,the article may comprise such active agent and may be used to apply andcontact such active agent to the treated skin area. Preferably, suchactive agent is effective in the treatment of a skin condition ordisorder or disease and/or useful in other dermatological uses.

Advantageously, such active agent may be introduced into the article,during the inventive method for treatment and/or during the inventivemethod of manufacturing: Such method may comprise a step ofpre-treatment of the article with an active agent, preferably performedbefore application of a BNC-containing article to the skin.Particularly, the article may be immersed in a composition and/or fluidcomprising the active agent, for example, a solution of fluid comprisingthe active agent, in an amount and time sufficient to enter the article,and, particularly, sufficient to release the active agent from thearticle to the skin during application in an effective amount,particularly a pharmaceutically and/or naturally and/or cosmeticallyand/or esthetically effective amount. The solution comprising the activeagent preferably is a fluid-soluble solution. The uptake of the activeagent from such solution into the article may be achieved by diffusionof the solution comprising the active agent into the article. However,additionally or alternatively, the article may be provided in anon-saturated form, i.e. having a fluid content below the maximum waterabsorption capacity of the article. Preferably, for such purpose, thearticle is provided having at least 1.5%, preferably at least 2%, morepreferably at least 3%, still more preferably at least 4%, still morepreferably at least 4.5%, still preferably at least 5% by weight, andmost preferably at least 10% by weight of BNC. Providing the articlewith water content below the maximum water absorption capacity of thearticle advantageously increases the uptake efficiency of the activeagent into the article, and reduces the amount of time, which isnecessary for pre-treatment of the article with such active agent.

A pharmaceutically active agent, which may be comprised in the article,generally can be any pharmaceutically active agent suitable for thetreatment of the respective skin condition, skin disorder or disease ordermatological use. Particularly, the pharmaceutically active agent maybe advantageously selected from the group comprising azelaic acid,antiacarians, local anesthetics, e.g. lidocaine, corticoids,antimycotics, e.g. benzylamine or its derivatives, for examplebutenafine hydrochloride, immune suppressives, antibiotics, preferablytetracycline or minocycline, and particularly erythromycin ormetronidazole, and wound caring products comprising wound-caringemulsions, e.g. cicalfate postacte, cold cream or antisepticalointments, or the like. Particularly, steroids of class 1 or 2 may beadvantageously applied. Pharmaceutically active agents, for ex-ample,erythromycin, azelaic acid, or metronidazole are particularly useful inthe treatment of skin disorders or diseases and skin conditions,particularly facial dermatitis, for example perioral dermatitis andperiorbital dermatitis, and may allow for a more rapid improvement.Corticoids are preferably avoided. However, also other pharmaceuticallyactive agents may be comprised in the article. For example, antibiotics,particularly tetracycline and minocycline, can provide a therapy forinflammatory skin disorder or dis-eases or conditions, particularly offacial dermatitis. Such pharmaceutically active agents usually have tobe applied repeatedly for several days or weeks.

The present invention allows for a relatively easy and comfortable wayto apply an active agent, particularly pharmaceutically active agent,comprised in the article. Thereby, also other active agents areconsidered in the present invention comprising naturally, cosmeticand/or esthetic active agents, particularly of plant-based or herbalorigin, for example from plant extracts and/or derivatives therefrom. Aparticularly preferred active agent is caffeine. The active agent maycomprise at least one tanning agent or tannin. A tannin or tanning agentaccording to the present invention preferably is selected from the groupcomprising tea drugs, preferably selected from the group comprisingcate-chines, pyrogallol-type tannins, and tannins of algae.Particularly, a tannin or tanning agent according to the presentinvention may be selected from the group comprising tannins oftannin-containing plants or plant parts, e.g. raspberry and/orblackberry leaves, oak tree, chestnut, acacia, lady's mantle(Alchemilla), witch-hazel leaves, grapes, black and green tea. Forexample, the article may comprise black tea and/or green tea and/ortanning agents of black tea and/or green tea, respectively. For thispurpose, the article may be immersed in black and/or green tea beforeapplication. Tanning agents, particularly of black or green tea, mayadvantageously improve the skin condition, disorder or disease. In orderto provide a sufficient amount of tanning agents, the tea is left todraw for at least 5 minutes, preferably at least 30 min, more preferablyat least 60 min. Subsequently, the tea can be cooled and the articleimmersed in the tea, as heat may have a disadvantageous effect oninflammation.

In some embodiments in which the treatment is a medical treatment themethod may comprise a step of applying photodynamic therapy to the areaof skin. Particularly, applying the BNC-containing article to the areaof skin may be carried out before and/or after the photodynamic therapyis applied. Preferably, the BNC-containing article is applied to thearea of skin at least after applying photodynamic therapy. Thisadvantageously allows for reduction of undesired side-effects ofphotodynamic therapy, and more particularly provides moisture andcooling to the treated area of skin. Preferably, the photodynamictherapy according to the present invention is a photodynamic therapyother than laser fracturing. Such photodynamic therapy may particularlybe useful in the treatment of skin conditions, diseases and disorders,particularly of psoriasis, acne, actinic keratosis or rosacea. Thepresent invention thus provides an advantageous use of the inventivearticle in the accompanying therapy of skin conditions, diseases anddis-orders of dermatological products or treatments.

In some embodiments in which the treatment is a non-medical treatment,the method may comprise an esthetic or cosmetic treatment, for examplefor wrinkle reduction. Particularly, the method may comprise a step ofesthetic or cosmetic treatment, prefer-ably selected from the groupcomprising subcutaneous injection of hyaluronic acid and calciumhydroxylapatite (filler) or botulinum toxin (Botox), applying needling(for example micro-needling), peeling (for example fruit acid peeling),abrasion or laser fractioning to the area of skin. Particularly,applying the BNC-containing article to the area of skin may be carriedout before and/or after the esthetic or cosmetic treatment is applied.Preferably, the BNC-containing article is applied to the area of skin atleast after applying an esthetic or cosmetic treatment. Thisadvantageously allows for reduction of un-desired side-effects of theesthetic or cosmetic treatment, for example swelling, and moreparticularly provides moisture and cooling to the treated area of skin.

The article can be advantageously designed such that its shape isadapted to the desired area of skin. In a preferred embodiment, thearticle is applied to the face or part of the face, e.g. the lid or rimof the eye, as the area of skin. The article can be provided in the formof a sheet, particularly a pad, preferably in the form of a mask,compress, bandage, dressing or patch or pads depending on the desiredarea of skin. This allows for a relatively easy application and providesan advantageous adaption on the skin. Preferably, the article isprovided in the form of a face mask, mouth mask, forehead mask, eye maskor eye pads.

A “face mask” as used herein, preferably is dimensioned to coveressentially the entire skin of the face of a subject. A “mouth mask” asused herein, preferably is dimensioned to cover essentially the entireskin of the lower part of the face of a subject, particularly comprisingmouth, cheeks, chin, and optionally a part of the throat. A “foreheadmask” as used herein, preferably is dimensioned to cover essentially theentire skin of the forehead of the face of a subject, however,preferably not the eyes. An “eye mask” as used herein, preferably isdimensioned to cover essentially both eyes of a subject, and optionallyat least the upper part of the nose. An “eye pad” as used herein,preferably is dimensioned to cover essentially one single eye of asubject. The term “eye pad” as used herein, preferably, refers to oneparticular dimension, i.e. adapted to cover essentially one single eyeof a subject. However, the article in the form of an eye pad is notrestricted to said particular form of use. More particularly, thepresent inventors have found that an article with the dimensioning andform of an eye pad as described herein, advantageously may also beapplied, particularly without any further modification, to the cornerarea of the mouth. Insofar, it is to be understood that the term “eyepad” may additionally provide the advantageous application of thearticle at the corner area of the mouth.

The article according to the present invention is of particularadvantage as it may be designed or provided such that it isself-adhering. Particularly, it adheres to the skin without any fixationmeans. Particularly, the article of the present invention can bedesigned relatively light weight and/or relatively small.

If it is referred herein to a “weight” or “weight per unit area”, the“weight” or “weight per unit area”, respectively, is preferablydetermined based on the mass of the article, or mass per unit area ofthe article, respectively. Said mass of the article, or mass per unitarea of the article, respectively, is preferably determined in a wetstate of the article, which is achieved by hot pressing of the articleuntil a cellulose content of 3-4% is reached, and subsequently the massof the article is determined.

The article of the present invention may preferably have a weight perunit area of at least 0.01 g/cm², preferably of at least 0.03 g/cm²,more preferably at least 0.04 g/cm², still more preferably at least 0.05g/cm². The article of the present invention may preferably have a weightper unit area of at most 1.00 g/cm², preferably of at most 0.30 g/cm2,more preferably at most 0.25 g/cm², still more preferably at most 0.20g/cm², still more preferably at most 0.175 g/cm², and most preferably atmost 0.170 g/cm². Particularly, the article of the present invention maypreferably have a weight per unit area of from at least 0.01 g/cm² to atmost 1.00 g/cm², more preferably from at least 0.01 g/cm² to at most0.30 g/cm², still more preferably from at least 0.01 g/cm² to at most0.25 g/cm², still more preferably from at least 0.01 g/cm² to at most0.20 g/cm², still more preferably from at least 0.01 g/cm² to at most0.175 g/cm², still more preferably from at least 0.01 g/cm² to at most0.170 g/cm², still more preferably from at least 0.03 g/cm² to at most1.00 g/cm², still more preferably from at least 0.03 g/cm² to at most0.30 g/cm², still more preferably from at least 0.03 g/cm² to at most0.25 g/cm², still more preferably from at least 0.03 g/cm² to at most0.20 g/cm², still more preferably from at least 0.03 g/cm² to at most0.175 g/cm², still more preferably from at least 0.03 g/cm² to at most0.170 g/cm², still more preferably from at least 0.04 g/cm² to at most1.00 g/cm², still more preferably from at least 0.04 g/cm² to at most0.30 g/cm², still more preferably from at least 0.04 g/cm² to at most0.25 g/cm², still more preferably from at least 0.04 g/cm² to at most0.20 g/cm², still more preferably from at least 0.04 g/cm² to at most0.175 g/cm², still more preferably from at least 0.04 g/cm² to at most0.170 g/cm², still more preferably from at least 0.05 g/cm² to at most1.00 g/cm², still more preferably from at least 0.05 g/cm² to at most0.30 g/cm², still more preferably from at least 0.05 g/cm² to at most0.25 g/cm², still more preferably from at least 0.05 g/cm² to at most0.20 g/cm², still more preferably from at least 0.05 g/cm² to at most0.175 g/cm², and most preferably from at least 0.05 g/cm2 to at most0.170 g/cm². Such densities support the self-adhering properties of thearticle. If the density is very high, gravitational forces may exceedself-adhering forces. However, if the density is very low, thedrapability of the article may be deteriorated. Drapability in the senseof the present invention is the ability of the article to be deformedand placed in a desired position without creation of unwanted creases orfolds. The reason for deterioration of drapability at low densities ofthe article is that the self-adhering forces may be very strong makingit very difficult or even impossible to put the article into an adequateposition without creating unwanted creases or even tearing the articleapart.

The width of an article of the present invention in the form of a facemask preferably is at least 175 mm, preferably at least 180 mm, morepreferably at least 185 mm. The width preferably is at most 280 mm, morepreferably at most 270 mm, still more preferably at most 250 mm,preferably at most 240 mm. The width preferably is at least 175 mm to atmost 280 mm, more preferably at least 175 mm to at most 270 mm, stillmore preferably at least 175 mm to at most 250 mm, still more preferablyat least 175 mm to at most 240 mm, still more preferably at least 180 mmto at most 280 mm, still more preferably at least 180 mm to at most 270mm, still more preferably at least 180 mm to at most 250 mm, still morepreferably at least 180 mm to at most 240 mm, still more preferably atleast 185 mm to at most 280 mm, still more preferably at least 185 mm toat most 270 mm, still more preferably at least 185 mm to at most 250 mm,and still more preferably at least 185 mm to at most 240 mm.

The article of the present invention in the form of a face maskpreferably has a height of at least 170 mm, preferably at least 175 mm.The height is preferably at most 200 mm, preferably at most 180 mm, morepreferably at most 175 mm. The height is preferably from at least 170 mmto at most 200 mm, more preferably from at least 170 mm to at most 180mm, still more preferably from at least 170 mm to at most 175 mm, stillmore preferably from at least 175 mm to at most 200 mm, still morepreferably from at least 175 mm to at most 180 mm, and still morepreferably from at least 175 mm to at most 175 mm.

The width-to-height ratio of the article of the present invention in theform of a face mask preferably is of at least 1.000, preferably of atleast 1.050, more preferably of at least 1.057. The width-to-heightratio of the article of the present invention in the form of a face maskpreferably is of at most 1.500, more preferably of at most 1.450, stillmore preferably of at most 1.425, and most preferably of at most 1.412.The width-to-height ratio of the article of the present invention in theform of a face mask preferably is from at least 1.000 to at most 1.500,more preferably from at least 1.000 to at most 1.450, still morepreferably from at least 1.000 to at most 1.425, still more preferablyfrom at least 1.000 to at most 1.412, still more preferably from atleast 1.050 to at most 1.500, still more preferably from at least 1.050to at most 1.450, still more preferably from at least 1.050 to at most1.425, still more preferably from at least 1.050 to at most 1.412, stillmore preferably from at least 1.057 to at most 1.500, still morepreferably from at least 1.057 to at most 1.450, still more preferablyfrom at least 1.057 to at most 1.425, and most preferably from at least1.057 to at most 1.412. Such ratios are advantageous for fitting thearticle to the face and for improving the self-adhering properties ofthe article. If the ratio is very high, the article only fits poorly tothe face. However, if the ratio is very low, self-adherence of thearticle to the skin is impaired. In summary, an adequate width-to-heightratio as described above is advantageous for handling, adhesion andfitting of the article.

The article of the present invention in the form of a face maskpreferably has a total weight of at most 120 g, preferably at most 80 g,more preferably at most 70 g, still more preferably at most 68.5 g,still more preferably at most 50 g, still more preferably at most 40 g,still more preferably at most 30 g, and still more preferably at most 28g.

The article of the present invention in the form of a face mask maypreferably have a weight per unit area of at least 0.03 g/cm²,preferably at least 0.04 g/cm², more preferably at least 0.05 g/cm².Thearticle of the present invention in the form of a face mask maypreferably have a weight per unit area of at most 0.25 g/cm², preferablyat most 0.20 g/cm², more preferably at most 0.17 g/cm². The article ofthe present invention in the form of a face mask may preferably have aweight per unit area of from at least 0.03 g/cm² to at most 0.25 g/cm²,more preferably from at least 0.03 g/cm² to at most 0.20 g/cm², stillmore preferably from at least 0.03 g/cm² to at most 0.17 g/cm², stillmore preferably from at least 0.04 g/cm² to at most 0.25 g/cm², stillmore preferably from at least 0.04 g/cm² to at most 0.20 g/cm², stillmore preferably from at least 0.04 g/cm² to at most 0.17 g/cm², stillmore preferably from at least 0.05 g/cm² to at most 0.25 g/cm², stillmore preferably from at least 0.05 g/cm² to at most 0.20 g/cm², and mostpreferably from at least 0.05 g/cm² to at most 0.17 g/cm².

In a particular preferred embodiment, an article of the presentinvention in the form of a face mask has an average thickness of about 2mm, and a width of about 185 mm, and a height of about 175 mm, and aweight of about 53 g, and a weight per unit area of from at least 0.14g/cm² to at most 0.17 g/cm². In a further particular preferredembodiment an article of the present invention in the form of a facemask has an average thickness of about 0.8 to 1.0 mm, and a width ofabout 185 mm, and a height of about 175 mm, and a weight of about 27 g,and a weight per unit area of from at least 0.05 g/cm² to at most 0.11g/cm². In another preferred embodiment an article of the presentinvention in the form of a face mask has an average thickness of about1.5 to 2.5 mm, and a width of about 250 mm, and a height of about 200mm, and an average weight of about 106 g, and a weight per unit area offrom at least 0.19 g/cm² to at most 0.25 g/cm². The indicated weightrefers to articles having a fluid content of 95% by weight.

The width of an article of the present invention in the form of a mouthmask preferably is at least 100 mm, preferably at least 110 mm, morepreferably at least 120 mm, most preferably at least 125 mm. The widthpreferably is at most 135 mm, preferably at most 130 mm, more preferablyat most 125 mm. The width preferably is at least 100 mm to at most 135mm, more preferably at least 100 mm to at most 130 mm, more preferablyat least 100 mm to at most 125 mm, still more preferably at least 110 mmto at most 135 mm, at least 110 mm to at most 130 mm, and still morepreferably at least 120 mm to at most 130 mm. The article of the presentinvention in the form of a mouth mask preferably has a height of atleast 75 mm, preferably at least 80 mm, more preferably at least 85 mm.The height is preferably at most 95 mm, more preferably at most 90 mm,still more preferably at most 85 mm. The width-to-height ratio of thearticle of the present invention in the form of a mouth mask preferablyis of at least 1.25, more preferably at least 1.30, still morepreferably at least 1.35, still more preferably at least 1.40, stillmore preferably at least 1.45, and most preferably at least 1.47. Thewidth-to-height ratio of the article of the present invention in theform of a mouth mask preferably is of at most 1.60, more preferably atmost 1.55, still more preferably at most 1.50, and most preferably atmost 1.47. The width-to-height ratio of the article of the presentinvention in the form of a mouth mask preferably is from at least 1.25to at most 1.60, more preferably from at least 1.25 to at most 1.55,still more preferably from at least 1.25 to at most 1.50, still morepreferably from at least 1.25 to at most 1.47, still more preferablyfrom at least 1.30 to at most 1.60, still more preferably from at least1.30 to at most 1.55, still more preferably from at least 1.30 to atmost 1.50, still more preferably from at least 1.30 to at most 1.47,still more preferably from at least 1.35 to at most 1.60, still morepreferably from at least 1.35 to at most 1.55, still more preferablyfrom at least 1.35 to at most 1.50, still more preferably from at least1.35 to at most 1.47, still more preferably from at least 1.40 to atmost 1.60, still more preferably from at least 1.40 to at most 1.55,still more preferably from at least 1.40 to at most 1.50, still morepreferably from at least 1.40 to at most 1.47, still more preferablyfrom at least 1.45 to at most 1.60, still more preferably from at least1.45 to at most 1.55, still more preferably from at least 1.45 to atmost 1.50, still more preferably from at least 1.45 to at most 1.47,still more preferably from at least 1.47 to at most at most 1.60, stillmore preferably from at least 1.47 to at most at most 1.55, and mostpreferably from at least 1.47 to at most 1.50. The article of thepresent invention in the form of a mouth mask preferably has a totalweight of at most 25 g, preferably at most 20,5 g, more preferably atmost 15 g, still more preferably at most 10 g, still more preferably atmost 8 g, and still more preferably at most 7.8 g. The article of thepresent invention in the form of a mouth mask may preferably have aweight per unit area of at least 0.03 g/cm², preferably at least 0.04g/cm², more preferably at least 0.05 g/cm², still more preferably atleast 0.06 g/cm². The article of the present invention in the form of amouth mask may preferably have a weight per unit area of at most 0,5g/cm², preferably at most 0.4 g/cm², more preferably at most 0.3 g/cm²,still more preferably at most 0.25 g/cm². The article of the presentinvention in the form of a mouth mask may preferably have a weight perunit area of from at least 0.03 g/cm² to at most 0,5 g/cm², morepreferably from at least 0.04 g/cm² to at most 0,5 g/cm², still morepreferably from at least 0.05 g/cm² to at most 0,5 g/cm², still morepreferably from at least 0.06 g/cm² to at most 0,5 g/cm², still morepreferably from at least 0.03 g/cm² to at most 0.4 g/cm², still morepreferably from at least 0.04 g/cm², to at most 0.4 g/cm², still morepreferably from at least 0.05 g/cm² to at most 0.4 g/cm², still morepreferably from at least 0.06 g/cm² to at most 0.4 g/cm², still morepreferably from at least 0.03 g/cm² to at most 0.3 g/cm², still morepreferably from at least 0.04 g/cm², to at most 0.3 g/cm², still morepreferably from at least 0.05 g/cm² to at most 0.3 g/cm², still morepreferably from at least 0.06 g/cm² to at most 0.3 g/cm², still morepreferably from at least 0.03 g/cm² to at most 0.25 g/cm², still morepreferably from at least 0.04 g/cm², to at most 0.25 g/cm², still morepreferably from at least 0.05 g/cm² to at most 0.25 g/cm², and mostpreferably from at least 0.06 g/cm² to at most 0.25 g/cm². In aparticular preferred embodiment, an article of the present invention inthe form of a mouth mask has an average thickness of about 2 mm, and awidth of about 125 mm, and a height of about 85 mm, and a weight ofabout 20 g and a weight per unit area of from at least 0.175 g/cm² to atmost 0.215 g/cm².

In a further particular preferred embodiment an article of the presentinvention in the form of a mouth mask has an average thickness of about1.0 mm, and a width of about 125 mm, and a height of about 85 mm, and aweight of about 7.65 g and a weight per unit area of from at least 0.060g/cm² to at most 0.085 g/cm². The width of an article of the presentinvention in the form of a forehead mask preferably is of at least 175mm, preferably of at least 180 mm, more preferably of at least 185 mm,most preferably of at least 190 mm. The width preferably is of at most200 mm, preferably of at most 195 mm, more preferably of at most 190 mm.The width preferably is of at least 175 mm to at most 200 mm, morepreferably of at least 175 mm to at most 195 mm, more prefer-ably atleast 175 mm to at most 190 mm, still more preferably of at least 185 mmto at most 200 mm, of at least 185 mm to at most 195 mm, and still morepreferably of at least 185 mm to at most 190 mm. The article of thepresent invention in the form of a forehead mask preferably has a heightof at least 50 mm, preferably at least 55 mm, more preferably at least60 mm. The height is preferably at most 70 mm, more prefer-ably at most65 mm, still more preferably at most 60 mm. The width-to-height ratio ofthe article of the present invention in the form of a forehead maskpreferably is of at least 3.1 and at most 3.2. The article of thepresent invention in the form of a forehead mask preferably has a totalweight of at most 25 g, preferably at most 22.5 g, more preferably atmost 21 g, still more preferably at most 15 g, still more preferably atmost 12.5 g, and still more preferably at most 11 g.

The article of the present invention in the form of a forehead mask maypreferably have a weight per unit area of at least 0.050 g/cm², morepreferably at least 0.060 g/cm2, still more preferably at least 0.070g/cm², and most preferably at least 0.080 g/cm2. The article of thepresent invention in the form of a forehead mask may preferably have aweight per unit area of at most 0.300 g/cm², more preferably at most0.250 g/cm², still more preferably at most 0.200 g/cm², and mostpreferably at most 0.190 g/cm². The article of the present invention inthe form of a forehead mask may preferably have a weight per unit areaof from at least 0.050 g/cm² to at most 0.300 g/cm², more preferablyfrom at least 0.050 g/cm² to at most 0.250 g/cm², still more preferablyfrom at least 0.050 g/cm² to at most 0.200 g/cm², still more preferablyfrom at least 0.050 g/cm² to at most 0.190 g/cm², still more preferablyfrom at least 0.060 g/cm² to at most 0.300 g/cm², still more preferablyfrom at least 0.060 g/cm² to at most 0.250 g/cm², still more preferablyfrom at least 0.060 g/cm² to at most 0.200 g/cm2, still more preferablyfrom at least 0.060 g/cm² to at most 0.190 g/cm², still more preferablyfrom at least 0.070 g/cm² to at most 0.300 g/cm², still more preferablyfrom at least 0.070 g/cm² to at most 0.250 g/cm2, still more preferablyfrom at least 0.070 g/cm² to at most 0.200 g/cm², still more preferablyfrom at least 0.070 g/cm² to at most 0.190 g/cm², still more preferablyfrom at least 0.080 g/cm² to at most 0.300 g/cm², still more preferablyfrom at least 0.080 g/cm² to at most 0.250 g/cm², still more preferablyfrom at least 0.080 g/cm² to at most 0.200 g/cm2, and most preferablyfrom at least 0.080 g/cm² to at most 0.190 g/cm².

In a particular preferred embodiment, an article of the presentinvention in the form of a forehead mask has an average thickness ofabout 2 mm, and a width of about 190 mm, and a height of about 60 mm,and a weight of about 20.0 g and a weight per unit area of from at least0.170 g/cm² to at most 0.190 g/cm².

In a further particular preferred embodiment an article of the presentinvention in the form of a forehead mask has an average thickness ofabout 1.0 mm, and a width of about 190 mm, and a height of about 60 mm,and a weight of about 10.75 g and a weight per unit area of from atleast 0.080 g/cm² to at most 0.190 g/cm².

The width of an article of the present invention in the form of an eyemask preferably is at least 185 mm, preferably at least 188 mm, morepreferably at least 190 mm, most preferably at least 191 mm. The widthpreferably is at most 195 mm, preferably at most 192.5 mm, morepreferably at most 191 mm. The width preferably is at least 185 mm to atmost 195 mm, more preferably at least 185 mm to at most 192.5 mm, morepreferably at least 185 mm to at most 191 mm, still more preferably atleast 190 mm to at most 195 mm, at least 190 mm to at most 192,5 mm, andstill more preferably at least 191 mm to at most 192.5 mm. The articleof the present invention in the form of an eye mask preferably has aheight of at least 55 mm, preferably at least 57.5 mm, more preferablyat least 60 mm. The height is preferably at most 65 mm, more preferablyat most 62.5 mm, still more preferably at most 60 mm. Thewidth-to-height ratio of the article of the present invention in theform of an eye mask preferably is of at least 3.15 and at most 3.25. Thearticle of the present invention in the form of an eye mask preferablyhas a total weight of at most 25 g, preferably at most 22.5 g, morepreferably at most 21 g, still more preferably at most 15 g, still morepreferably at most 12.5 g, and still more preferably at most 11 g.

The article of the present invention in the form of an eye mask maypreferably have a weight per unit area of at least 0.050 g/cm², morepreferably at least 0.060 g/cm², still more preferably at least 0.070g/cm², and most preferably at least 0.080 g/cm². The article of thepresent invention in the form of an eye mask may preferably have aweight per unit area of at most 0.400 g/cm², more preferably at most0.350 g/cm², still more preferably at most 0.300 g/cm², and mostpreferably at most 0.250 g/cm². The article of the present invention inthe form of a eye mask may preferably have a weight per unit area offrom at least 0.050 g/cm² to at most 0.400 g/cm², more preferably fromat least 0.050 g/cm2 to at most 0.350 g/cm², still more preferably fromat least 0.050 g/cm² to at most 0.300 g/cm2, still more preferably fromat least 0.050 g/cm² to at most 0.250 g/cm², still more preferably fromat least 0.060 g/cm² to at most 0.400 g/cm², still more preferably fromat least 0.060 g/cm2 to at most 0.350 g/cm², still more preferably fromat least 0.060 g/cm² to at most 0.300 g/cm², still more preferably fromat least 0.060 g/cm² to at most 0.250 g/cm², still more preferably fromat least 0.070 g/cm² to at most 0.400 g/cm², still more preferably fromat least 0.070 g/cm² to at most 0.350 g/cm², still more preferably fromat least 0.070 g/cm² to at most 0.300 g/cm², still more preferably fromat least 0.070 g/cm² to at most 0.250 g/cm², still more preferably fromat least 0.080 g/cm2 to at most 0.400 g/cm², still more preferably fromat least 0.080 g/cm² to at most 0.350 g/cm², still more preferably fromat least 0.080 g/cm² to at most 0.300 g/cm², and most preferably from atleast 0.080 g/cm² to at most 0.250 g/cm2.

In a particular preferred embodiment, an article of the presentinvention in the form of an eye mask has an average thickness of about 2mm, and a width of about 191 mm, and a height of about 60 mm, and aweight of about 23.20 g and a weight per unit area of from at least0.175 g/cm2 to at most 0.250 g/cm2. In a further particular preferredembodiment an article of the present invention in the form of an eyemask has an average thickness of about 1.0 mm, and a width of about 190mm, and a height of about 60 mm, and a weight of about 11.0 g and aweight per unit area of from at least 0.080 g/cm² to at most 0.110g/cm². The width of an article of the present invention in the form ofan eye pad preferably is of at least 67.5 mm, preferably of at least 70mm, more preferably of at least 72.5 mm, most preferably of at least 75mm. The width preferably is of at most 80 mm, preferably of at most 77.5mm, more preferably of at most 75 mm. The width preferably is of atleast 67.5 mm to at most 80 mm, more preferably of at least 67.5 mm toat most 77.5 mm, more preferably at least 67.5 mm to at most 75 mm,still more preferably of at least 72.5 mm to at most 77.5 mm, of atleast 72.5 mm to at most 75 mm. The article of the present invention inthe form of an eye pad preferably has a height of at least 30 mm,preferably at least 32.5 mm, more preferably at least 35 mm. The heightis preferably at most 40 mm, more preferably at most 37.5 mm, still morepreferably at most 35 mm. The width-to-height ratio of the article ofthe present invention in the form of an eye pad preferably is of atleast 2.1 and at most 2.2. The article of the present invention in theform of an eye pad preferably has a total weight of at most 3.5 g,preferably at most 3.0 g, more preferably at most 2.8 g, still morepreferably at most 2.75 g.

The article of the present invention in the form of an eye pad maypreferably have a weight per unit area of at least 0.055 g/cm², morepreferably at least 0.065 g/cm², and most preferably at least 0.075g/cm². The article of the present invention in the form of an eye padmay preferably have a weight per unit area of at most 0.120 g/cm², morepreferably at most 0.135 g/cm², and most preferably at most 0.140 g/cm².The article of the present invention in the form of a eye pad maypreferably have a weight per unit area of from at least 0.055 g/cm² toat most 0.120 g/cm², more preferably from at least 0.055 g/cm² to atmost 0.135 g/cm², still more preferably from at least 0.055 g/cm² to atmost 0.140 g/cm², still more preferably from at least 0.065 g/cm² to atmost 0.120 g/cm², still more preferably from at least 0.065 g/cm² to atmost 0.135 g/cm², still more preferably from at least 0.065 g/cm² to atmost 0.140 g/cm², still more preferably from at least 0.075 g/cm² to atmost 0.120 g/cm², still more preferably from at least 0.075 g/cm² to atmost 0.135 g/cm², and most preferably from at least 0.075 g/cm² to atmost 0.140 g/cm².

In a particular preferred embodiment, an article of the presentinvention in the form of an eye pad has an average thickness of about1.0 to 2.0 mm, and a width of about 75 mm, and a height of about 35 mm,and a weight of about 2.75 g and a weight per unit area of from at least0.140 g/cm² to at most 0.120 g/cm².

Terms like “height” or “width” of an article as used herein preferablyrefer to the largest respective expansion of the article in its positionof intended use. For example, the terms “height” or “width” determinethe respective largest expansion of the article, as if placed on theface of a subject. The term “width” of an article as used herein,preferably refers to the largest expansion of the article in lateraldirection, e.g. from ear to ear, whereas the term “height” preferablyrefers to the largest expansion of the article in a position of itsintended use in cranial-caudal direction.

Particularly, the inventive method for treatment in step a. may compriseadhering of the article to the skin by adhesion, and preferably withoutany fixation means. This allows a subject applying the article to moveunimpededly while the article remains on the area of skin, even if thepredetermined period of time is relatively long. It is the merit of thepresent inventors that the advantageous adhesion of an article accordingto the present invention is depending on a variety of parameters, ratherthan one parameter alone. Particularly, such parameters are theadvantageous surface characteristics of the inventive article, therelatively low weight of the articles of the present invention, theadvantageously high tensile strength, which allows a better adaption tothe skin and face structures.

The present inventors have found that the article and the method fortreatment of the present invention advantageously provides a soothing,cooling, caring, and alleviative effect to an area of skin by applyingthe article to the skin. Particularly, applying the article to the skinmay reduce pain, skin irritation or spanning of the skin while thearticle remains on the area of skin and provides a moisturizing effectwithout wet feeling. Thereby the article and the method are particularlyuseful in the treatment of skin dis-eases, conditions and disorders,particularly all forms of dermatitis and more particularly in thetreatment of facial dermatitis, e.g. perioral, periorbital, periocularor perinasal dermatitis; however, also of psoriasis, acne or rosacea.Advantageously, the article and the method of the present inventionallow for reduction of the itchiness of the skin, and thus may reducethe desire of the subject to itch the area of the skin. Moreover, thearticle and the method of the present invention advantageously increasephysical com-fort and self-adhering, which allows the subject tocomfortably and freely move during application of the article to thearea of skin. Still further the article and method advantageouslyreduces swellings and skin redness, and erythema.

The inventive article and method may in general be applied to anysubject in need thereof, particularly a subject suffering from a skindisease, disorder or condition. However, preferably the subject is amammal, in particular a human, preferably a human female.

According to the inventive method for treatment the article is left onthe skin for a pre-determined time period. To achieve the desiredadvantageous effects it is preferred that the time period is not tooshort. The predetermined time period preferably is at least 10 minutes,at least 15 minutes, at least 20 minutes, at least 30 minutes, at least1 hour, at least 2 hours, or at least 3 hours. However, in order toprevent discomfort or effects of over-use, it is preferred that the timeperiod is not too long. The predetermined time period preferably is atmost 12 hours, preferably at most 10 hours, more preferably at most 8hours, still more preferably at most 5 hours, or still more preferablyat most 4 hours. In connection therewith, a person skilled in the artwill immediately understand that an article having higher fluid contentmay provide moisture in general for a longer time period. Thereby, ahigher water absorption capacity (WAC) is preferred, which in generalallows for a longer time period of efficient application.

A particularly advantageous effect may be achieved, if the article isapplied or the method is performed repeatedly for a treatment interval.A continuously repeated application is of advantage in order to achieveand improve the positive effects on the skin. Thereby it is preferredthat in a treatment interval steps a. to c., and optionally a step ofpre-treatment of the article, of the method for treatment are performedat least once within 24 hours. In an embodiment the treatment intervalis at least 1 day, at least 2 days, at least 3 days or at least 4 days.It is particularly preferred that during said treatment interval thesubject does not apply cosmetics and skin-care products other than theproduct of the present invention. This may advantageously initiate andsupport the natural healing process. However, the treatment intervalshould also not be too long. Preferably, the treatment interval is up to1 year, up to 6 months, up to 3 months, up to 1 month, up to 2 weeks orup to 1 week.

A particularly preferred application of the present invention in whichphotodynamic therapy is applied to the subject, it is preferred that thesteps a. to c., and optionally a step of pre-treatment of the article,of the inventive method are performed for a first time at most 1 hourafter a step of applying photodynamic therapy to the area of skin,wherein the predetermined time period is from at least 30 min to at most60 min; and additionally and subsequently, the steps a. to c., andoptionally a step of pre-treatment of the article, are performed atleast once within 24 hours during a treatment interval of at least 5days and at most 7 days, wherein the predetermined time period is fromat least 3 hours to at most 4 hours. It is known in the art thatpatients which are subjected to photodynamic therapy usually do notsuffer from pain during the application of photodynamic therapy.However, the burning effects of the treatment usually appear on the dayafter the photodynamic therapy treatment. With the article of thepresent invention applied to a subject for a first time at most 1 hourafter a step of applying photodynamic therapy the burning effects due tothe photodynamic therapy treatment can advantageously be reduced,already in advance.

Such scheme of application is particularly useful and effective, as thefirst application of the product within one hour after photo-therapytreatment allows an immediate effect of the inventive product. Thefurther applications of the product additionally and subsequent to saidfirst application can advantageously be performed without help orsupervision of a medical professional, particularly by the subjectitself.

The article of the present invention is particularly advantageous as itis of relatively light weight and has very soft and smooth surface feel.Particularly, the article provides an alleviating effect on skin thatsuffers from skin diseases, disorders and conditions, particularly burnsand all forms of dermatitis. Moreover, the article advantageously isbiodegradable and can be produced by a very economical method.

In a still further aspect the above described problems are alsoadvantageously solved by a method of manufacturing a BNC-containingarticle according to the present invention.

In connection therewith it is important to understand that the method ofmanufacturing of the article according to the present invention shows astrong influence on various parameters of the article, whichparticularly also influence the efficacy of treatment and provides itsadvantageous properties. Particularly, the method of manufacturing mayhave an impact on the fibers of the BNC and their average diameter, thesum of the constituents fluid and BNC, the mass ratio of BNC lα to BNClβ, the volumetric mass density, the molecular mass, the amount ofcarbonyl groups, the polydispersity index (M_(w)/M_(n)), thecrystallinity Ic, the water absorption capacity, the water retentioncapacity and/or the tensile strength of the BNC, and of theBNC-containing article, respectively.

The method of manufacturing comprises at least the following steps: a.)providing BNC in a continuous semi-static process, b.) providing thearticle according to the present invention; and c.) optionallysterilizing the article.

Particularly, a step a) of providing BNC in a continuous semi-staticprocess may comprise providing the BNC as a BNC fleece. The terms“fleece” and “non-woven” are used interchangeably in the presentdescription. Particularly, step b.) of providing the article accordingto the present invention may comprise a step of cutting the article, inparticular with a jet of fluid into form, e.g. eye pad, forehead mask,eye mask, face mask, or the like. The fluid jet preferably is providedwith a pressure of at least 1000 and at most 4000 bar. The fluid jetpreferably has a diameter of from 100 μm to 300 μm, more preferably offrom 125 μm to 200 μm, most preferably of about 150 μm. Such cuttingwith a fluid jet is advantageous compared to cutting methods usuallyprovided in the art, for example, thermal cutting with a laser or thelike, or mechanical cutting. Such methods of the prior art usuallycompromise the structure of the BNC material. The cutting ac-cording tothe present invention, however, provides a high quality of the cuttingedge without destruction of the surrounding BNC.

The method of manufacturing according to the present inventionoptionally comprises a step c.) of sterilizing the article. Saidsterilizing step preferably comprises application of beta-irradiation,for example e-beam. This is advantageous as the number of radicals,which usually are generated using gamma-irradiation applied in the art,are not formed or reduced. This is particularly the case, as theapplication of beta-irradiation may allow for shorter treatment.

The method of manufacturing of the article according to the presentinvention comprises a continuous semi-static process of providingbiotechnologically produced nano-structured cellulose (BNC). It isparticularly preferred that the BNC is not produced in a static ordiscontinuous process. A “continuous semi-static” process as usedherein, preferably refers to a method in which the BNC is produced froma bacterial culture in a cultivation medium, which is not activelystirred, shacked, or otherwise moved during BNC synthesis, in which,however, the BNC is continuously produced by the bacterial culture. Thefact that the cultivation medium is not actively stirred, shacked, orother-wise moved during BNC synthesis does neither exclude harvesting orremoval of BNC from the bacterial culture and/or reaction vessel duringBNC synthesis nor adding cultivation medium and/or constituents of thecultivation medium during BNC biosynthesis. Particularly, in a“continuous semi-static” process as used herein, preferably the BNC isharvested or removed from the bacterial culture and/or reaction vesselmore than once during BNC synthesis, particularly regularly, step-wiseand/or continuously. Particularly, in a “continuous semi-static” processas used herein, preferably the cultivation medium and/or constituents ofthe cultivation medium are added more than once, preferably regularly,step-wise and/or continuously during the BNC synthesis. In connectiontherewith a “continuous semi-static” process as used herein, preferablyis not a batch production method.

In an embodiment of the “continuous semi-static” process, up to 1 m²,preferably up to 2.5 m², more preferably up to 5 m² of BNC is harvestedor removed from the bacterial culture and/or reaction vessel per day,particularly regularly, step-wise and/or continuously.

The advantageous properties and features, for example the advantageousadhesion properties or relatively light weight, of the article, of thisinvention, particularly of the BNC content of the article, can beadjusted by choosing suitable culturing conditions. The BNC content ofthe article according to the present invention preferably is produced inthe form of a BNC fleece.

Particularly, step a) of providing BNC in a continuous semi-staticprocess may comprise at least one of the following steps:

-   -   a′) providing a reaction vessel comprising cultivation medium;    -   a″) inoculating the cultivation medium with a BNC-producing        bacterial strain; and/or    -   a′″) bacterial synthesis of BNC in the reaction vessel.

Production of the BNC can preferably be done at a cell count of from 10⁴to 10⁷ cells/ml of culturing medium during the culturing. Preferably, astep a″) of inoculating the cultivation medium with a BNC-producingbacterial strain comprises providing a stock culture having about 10⁶cells/ml and inoculating the cultivation medium with the stock cultureresulting in a cell concentration of about 5x10³ cells/ml. Theproperties of the obtained BNC content of the article may also beinfluenced by the volume ratio of the cultivation medium to thebacterial strain stock culture used for inoculation. Preferably, thevolume ratio is at least 2:1, more preferably at least 5:1, morepreferably at least 10:1, and more preferably at least 15:1. Preferably,the volume ratio is at most 50:1, more preferably at most 30:1, and morepreferably at most 20:1.

Preferably, at least step a′″) of bacterial synthesis of BNC comprisesadding cultivation medium, or preferably selectively adding ingredientsof the cultivation medium, into the reaction vessel more than once,preferably regularly, step-wise and/or continuously during BNCsynthesis. Particularly, at least step a′″) of bacterial synthesis ofBNC in the reaction vessel preferably comprises incubating a bacterialculture in a cultivation medium, which is not actively stirred, shacked,or otherwise moved during BNC synthesis. The fact that the cultivationmedium is not actively stirred, shacked, or otherwise moved during BNCsynthesis does neither exclude harvesting or removal of BNC from thebacterial culture and/or reaction vessel during BNC synthesis nor addingcultivation medium and/or constituents of the cultivation medium duringBNC biosynthesis. Additionally or alternatively, at least step a′″) ofbacterial synthesis of BNC in the reaction vessel preferably comprisescontinuously producing BNC. Additionally or alternatively, at least stepa′″) of bacterial synthesis of BNC in the reaction vessel preferablycomprises harvesting and/or removing BNC from the bacterial cultureand/or reaction vessel during BNC syn-thesis more than once, preferablyregularly, step-wise and/or continuously during BNC synthesis.Additionally or alternatively, at least step a′″) of bacterial synthesisof BNC in the reaction vessel preferably comprises adding cultivationmedium and/or constituents of the cultivation medium to the bacterialculture and/or reaction vessel more than once, preferably regularly,step-wise and/or continuously during the BNC synthesis.

The properties of the obtained BNC content of the article may also beinfluenced by the composition of the cultivation medium. Preferably, thecultivation medium comprises a carbon source, a nitrogen source and avitamin source and optionally a buffer system. Preferably, the carbonsource is selected from one or more sugars and their derivatives.Preferably, the nitrogen source is peptone. Preferably, the vitaminsource is yeast extract. Preferably, the buffer system is disodiumhydrogen phosphate and citric acid.

Preferably, the cultivation medium is liquid.

Preferably, the cultivation medium comprises the carbon source in anamount of least 10 g/l, more preferably at least 15 g/l based on thevolume of the cultivation medium. Preferably, the cultivation mediumcomprises the carbon source in an amount of at most 30 g/l, morepreferably at most 25 g/l based on the volume of the cultivation medium.Particularly preferably, the cultivation medium comprises the carbonsource in an amount of about 20 g/l.

Preferably, the cultivation medium comprises the nitrogen source in anamount of least 2 g/l, more preferably at least 4 g/l based on thevolume of the cultivation medium. Preferably, the cultivation mediumcomprises the nitrogen source in an amount of at most 10 g/l, morepreferably at most 7 g/l based on the volume of the cultivation medium.Particularly preferably, the cultivation medium comprises the nitrogensource in an amount of about 5 g/l.

Preferably, the cultivation medium comprises the vitamin source in anamount of least 2 g/l, more preferably at least 4 g/l based on thevolume of the cultivation medium. Preferably, the cultivation mediumcomprises the vitamin source in an amount of at most 10 g/l, morepreferably at most 7 g/l based on the volume of the cultivation medium.

Particularly preferably, the cultivation medium comprises the vitaminsource in an amount of about 5 g/l.

Preferably, the cultivation medium comprises the buffer system in anamount of least 2 g/l, more preferably at least 4 g/l based on thevolume of the cultivation medium. Preferably, the cultivation mediumcomprises the buffer system in an amount of at most 10 g/l, morepreferably at most 5 g/l based on the volume of the cultivation medium.Particularly preferably, the cultivation medium comprises the buffersystem in an amount of about 4.5 g/l.

Particularly, the cultivation medium comprises 20 g/l glucose, 5 g/lpeptone, 5 g/l yeast extract, 3.4 g/l disodium hydrogen phosphate and1.15 g/l citric acid.

Particularly, the cultivation medium is free of ginseng extracts.

The properties of the obtained BNC content of the article may also beinfluenced by the cultivation temperature. Preferably, the cultivationtemperature is at least 20° C., more preferably at least 25° C., morepreferably at least 28° C. If the cultivation temperature is too low,the bacterial strains do not grow properly. Preferably, the cultivationtemperature is at most 36° C., more preferably at most 33° C., morepreferably at most 30° C. If the cultivation temperature is too high,the bacterial strains do not grow properly.

The properties of the obtained BNC content of the article may also beinfluenced by the cultivation time. Preferably the cultivation time isat least 1 day, more preferably at least 3 days, still more preferablyat least 7 days, and still more preferably at least 10 days. If thecultivation time is too short, not enough cellulose is produced.Preferably, the cultivation time is at most 1 year, more preferably atmost 6 month, still more preferably at most 30 days, still morepreferably at most 25 days, and still more preferably at most 20 days.Particularly, a semi-static continuous process as described herein, mayallow for advantageously long cultivation times, during which, morepreferably the BNC is harvested or removed from the bacterial cultureand/or reaction vessel more than once during BNC synthesis, particularlyregularly, step-wise and/or continuously.

The properties of the obtained BNC content of the article may also beinfluenced by the culture volume. Preferably, the culture volume is atleast 20 ml, more preferably at least 500 ml, still more preferably atleast 2000 ml, still more preferably at least 4000 ml, and still morepreferably at least 10,000 ml. Preferably, the culture volume is at most200 l, more preferably at most 180 l, more preferably at most 100 l, andstill more preferably at most 50 l. Particularly, the semi-staticcontinuous process as described herein may allow for advantageously highculture volumes.

The culture volumes particularly may also depend on the desired BNCsynthesis area, and vice versa. The properties of the obtained BNCcontent of the article may also be influenced by the cultivation vesseland/or synthesis area. Preferably, the cultivation vessel has asynthesis area of at least 1 cm², more preferably at least 10 cm², morepreferably at least 100 cm², and still more preferably at least 10 m².Preferably, the cultivation vessel has a synthesis area of at most50,000 cm², more preferably at most 20,000 cm², more preferably at most1,000 cm², still more preferably at most 50 m², still more preferably atmost 100 m². Particularly, the semi-static continuous process asdescribed herein may allow for an advantageously high synthesis area,

The cellulose of the inventive article is biotechnologically producednano-structured cellulose, also referred to as “BNC” herein. In general,any cellulose-producing bacterial strain may be applied in the presentinvention. However, the BNC of the article of the present inventionpreferably is of the strain Komatagaibacter xylinum, also known asAcetobacter xylinum.

Preferably, the K. xylinum strain is selected from the group comprisingATCC 11142 and DSM 14666.

The BNC fleece produced by the method according to the present inventionmay advantageously be used directly as the article of the presentinvention or as the BNC content of the article according to the presentinvention.

Particularly, the cellulose-containing article comprises cellulose in anamount of at most 10%, preferably of at most 5% by weight.

The sum of fluid and cellulose, in the article, preferably is at least80% by weight, in particular at least 90% by weight, in particular atleast 95% by weight. In an embodiment the sum of the constituents fluidand cellulose in the article, preferably are essentially 100%. In otherwords, the article may essentially consist of a BNC fleece of fluid andcellulose, It is of particular advantage that the article as such candirectly be used in skin application, particularly without the need forfurther supporting or fixing means.

The term “fluid” as used herein, preferably refers to water and/or awater-based fluid comprising water, particularly de-ionized water, in anamount of at least 80%, preferably at least 90%, more preferably atleast 95%, still more preferably at least 99%, and still more preferablyat least 99.9%, and still more preferably 100%.

A relatively low average thickness of the article allows for aconvenient application by the subject. However, an article having anaverage thickness, which is too low, may more easily tear. The thicknessof the article preferably is in average at least 0.5 mm, more preferablyat least 0.8 mm, still more preferably at least 1.0 mm, still morepreferably at least 1.5 mm, and still more preferably at least 2.0 mm.On the other hand, an article having an average thickness, which is toohigh, may cause an uncomfortable feeling and may not adhere to the skinwithout the need for further adherence or fixation means. The averagethickness of the article preferably is at most 8.0 mm, more preferablyat most 6.0 mm, still more preferably at most 5.0 mm. The averagethickness of the article can be determined by usual methods known to theperson skilled in the art, comprising e.g. vernier caliper measurements.The BNC characteristics allow for thin articles at good tensilestrength.

Preferably, the article is a non-woven of fibers of the cellulose. Thisadvantageously allows a relatively easy and cost-effective production.Particularly, the fibers of the cellulose have an average diameter offrom 30 to 250 nm. The diameter is preferably determined from scanningelectron microscopy (SEM) pictures.

The volumetric mass density of the article, particularly of thecellulose content of the article, is at least 0.50 g/cm³, preferably atleast 0.55 g/cm³. The volumetric mass density of the article,particularly of the cellulose content of the article, is at most 1.50g/cm³, preferably at most 1.25 g/cm³.

The volumetric mass density of the article, particularly of thecellulose content of the article, preferably is from at least 0.50 g/cm³to at most 1.50 g/cm³, more preferably from at least 0.55 g/cm³ to atmost 1.50 g/cm3, still more preferably from at least 0.50 g/cm³ to atmost 1.25 g/cm³, and most preferably from at least 0.55 g/cm³ to at most1.25 g/cm3.

In order to achieve a density that is required to obtain optimumadhesion of the article to the skin the amount of bacteria andnutritional compositions in the culturing medium can be advantageouslyadjusted.

The weight-average molecular weight M_(w) of the article, particularlyof the cellulose of the article, preferably is at most 1,500,000 g/mol,more preferably at most 1,200,000 g/mol, more preferably at most1,000,000 g/mol, more preferably at most 900,000 g/mol, at most 850,000g/mol, at most 800,000 g/mol, most preferably at most 780,000 g/mol. Ifthe weight-average molecular weight M_(w) is very high, the stability ofthe material may be impaired. The weight-average molecular weight M_(w)of the article, particularly of the cellulose of the article, preferablyis at least 100,000 g/mol, preferably at least 250,000 g/mol, at least300,000 g/mol, at least 400,000 g/mol, most preferably at least 500,000g/mol. If the weight-average molecular weight M_(w) is very low, thedesired poly-dispersity index may not be achieved as described below.

The number-average molecular weight M_(n) of the article, particularlyof the cellulose of the article, preferably is at most 500,000 g/mol,preferably at most 400,000 g/mol, at most 450,000 g/mol, at most 400,000g/mol, most preferably at most 360,000 g/mol. If the number-averagemolecular weight M_(n) is very high, the desired polydispersity indexmay not be achieved as described below. The number-average molecularweight M_(n) of the article, particularly of the cellulose of thearticle, preferably is at least 100,000 g/mol, preferably at least150,000 g/mol, at least 200,000 g/mol, at least 250,000 g/mol, mostpreferably at least 300,000 g/mol. If the number-average molecularweight M_(n) is very low, the stability of the material may be impaired.

The degree of polymerization is the average number of monomeric units inthe BNC polymers of a specific BNC network. It can be expressed as theratio of the number-average molecular weight of the respective BNCpolymers to the molecular weight of the monomeric unit.

The polydispersity index (PDI) is a measure of the heterogeneity of themolecular mass distribution of the BNC polymers of a respective BNCnetwork. It is calculated as the ratio of the weight-average molecularweight to the number-average molecular weight of the respective BNCpolymers. Higher PDI values indicate a broader molecular weightdistribution of the BNC polymers of a BNC network. The length of thecellulose chains of the article are preferably relatively uniform, whichmay be reflected by a relatively low polydispersity index (M_(w)/M_(n)).

The PDI (M_(w)/M_(n)) of the article preferably is low. It is known thatat a relatively low PDI refers to a more stable material and porestructure. A PDI of nearly 1 would reflect a homogenicity which isnearly optimal. According to at least some embodiments, preferably thepolydispersity index PDI (M_(w)/M_(n)) of the article is less than 3.5,preferably less than 3.0, more preferably less than 2.75 and still morepreferably less than 2.5, still more preferably less than 2.0, stillmore preferably less than 1.75, and most preferably less than 1.5.

According to at least some embodiments, preferably the article ischaracterized by a DPn of at least 1,000, more preferably at least1,500, more preferably at least 1,700. Preferably, the article ischaracterized by a DPn of at most 5,000, more preferably at most 3,000,still more preferably at most 2,500, still more preferably at most2,200.

Preferably the article according to the present invention comprisesglycerin in an amount of at most 30% by weight, more preferably of atmost 15% by weight, still more preferably at most 10% by weight, mostpreferably of at most 5% by weight. In one particular embodiment, thearticle according to the present invention comprises no glycerin.Glycerin may disadvantageously result in unwanted material properties,particularly a higher weight of the article.

The cellulose content of the article preferably comprises carbonylgroups in an amount of less than 8.5 μmol/g, preferably of less than 8.0μmol/g, more preferably of less than 7.5 μmol/g, still more preferablyof less than 7.0 μmol/g, still more preferably of less than 6.0 μmol/g,and still more preferably of less than 5.75 μmol/g. The cellulosecon-tent of the article preferably comprises carbonyl groups in anamount of at least 1.0 μmol/g, more preferably of at least 1.5 μmol/g,still more preferably of at least 2.0 μmol/g, still more preferably ofat least 2.5 μmol/g, and most preferably of at least 2.75 μmol/g.

For cellulose, particularly, cellulose-containing articles, thecrystallinity Ic is an important parameter. The degree of crystallinityis preferably determined by NMR spectroscopy. A low crystallinity Ic mayparticularly be accompanied by a decrease in the permeability for gasesand liquids. For the purpose of the present invention, particularly theinventive article and its use in the inventive method of treatment, arelatively high crystallinity Ic is desired, in order to provide arelatively high permeability for gases and liquids. The crystallinity Icof the cellulose of the article is at least at least 55%, morepreferably at least 60%, more preferably at least 65%, more preferablyat least 70, most preferably at least 80%. Preferably, all crystallinityIc of the cellulose of the article is at most 95%, more preferably atmost 90%, more preferably at most 85%.

A person skilled in the art will recognize that BNC exists in severalcrystalline polymorphs. Moreover, BNC simultaneously crystallizes in aone-chain triclinic structure lα, and a two-chain modification lβ. Bothpolymorphs are packed in a parallel chain arrangement, but of variousratios in a cellulose-containing article, depending on the origin andmethod of manufacturing. Preferably, the cellulose of the inventivearticle comprises cellulose lα in an amount of at least 10%, preferablyat least 20%, more preferably at least 30% by weight of the article.Preferably, the cellulose of the inventive article comprises celluloselα in an amount of at most 90%, preferably at most 70%, more preferablyat most 50% by weight of the article. Additionally or alternatively, thecellulose of the inventive article comprises cellulose lβ in an amountof at least 1%, preferably at least 5%, more preferably at least 10% byweight. Preferably, the cellulose of the inventive article comprisescellulose lβ in an amount of at most 90%, preferably at most 80%, morepreferably at most 70%, still more preferably at most 60%, still morepreferably at most 50%, and most preferably at most 45% by weight.Preferably, the amount of cellulose lα and lβ is determined on the basisof CP/MAS 13C NMR. The above ranges are preferable to achieve thedesired properties of the article.

Particularly, the inventive article may comprise cellulose lα andcellulose lβ in a mass ratio of at most 2.75, preferably at most 2.5,more preferably at most 2.4. Preferably, the inventive article comprisescellulose lα and cellulose lβ in a mass ratio of at least 1.5,preferably at least 2.0, more preferably at least 2.25. The above ratiosare preferable to achieve the desired properties of the article.

For the purpose of the present invention the article provides fluid,particularly water, and optionally at least one active agent, to thetreated area of skin. A preferable water absorption capacity (WAC)and/or a preferable water retention capacity of the article may allowfor an increase in the desired effect of treatment. Particularly, theinventive article may have a water absorption capacity (WAC) of at least80%, more preferably at least 120%, more preferably at least 150%. Asdescribed herein, the water absorption capacity is calculated by thefollowing formula

WAC=mass(wet)/mass (dry)*100%.

Preferably, the article has a water absorption capacity (WAC) of at most300%, more preferably at most 250%, and still more preferably at most200%. Optionally and preferably, the article has a water absorptioncapacity (WAC) of from 150% to 200%. The water retention capacity (WRC)of the inventive article may be of at least 500%, preferably at least600%, more preferably at least 700%, most preferably at least 750%. Thewater retention capacity (WRC) of the inventive article may be of atmost 1,500%, preferably at most 1,250%, more preferably at most 1,000%,most preferably at most 950%. The water retention capacity (WRC) as usedherein is the ratio of wet mass at maximum WAC and dry mass determinedafter centrifugation of the article for 15 min at 5,000 rpm.

Preferably, the article has a moist vapor transmission rate in the wetstate of at least 100 g/(m²*24h), more preferably at least 200g/(m²*24h), more preferably at least 500 g/(m²*24h). Preferably, themulti-phase biomaterials have a moist vapor transmission rate in the wetstate of at most 3,000 g/(m²*24h), more preferably at most 2,000g/(m2*24h), more preferably at most 1,000 g/(m²*24h). Particularlypreferably, the multi-phase biomaterials have a moist vapor transmissionrate in the wet state of from 500 g/(m²*24h) to 1,000 g/(m²*24h).Preferably, the moist vapor transmission rate is determined according toDIN EN 13726-2:2002.

In order to provide an article which advantageously adapts to the skinarea to be treated, particularly to the geometry and dimensions of theface, the tensile strength of the article is of importance.Particularly, a too low tensile strength will not allow that the articleis stretchable and thus will not allow that the article adapts to theunevenness of the skin, particularly the unevenness of the face. Thetensile strength of the inventive article preferably is more than 100MPa, preferably more than 252 MPa, preferably more than 275 MPa, morepreferable more than 300 MPa, and most preferably of more than 310 MPa.The tensile strength of the inventive article preferably is less than1,000 MPa, preferably less than 750 MPa, more preferably less than 500MPa, and most preferably of less than 400 MPa. The tensile strength asreferred to herein preferably is determined after hot pressing of thearticle using a TIRAtest 2710 universal measuring device with a nominalforce of 1.5 kN. Preferably, the tensile strength as referred to hereinis determined according to DIN EN ISO 527-1:2012-06 and/or DIN EN ISO527-2:2012-06.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be described in further detail with referenceto the drawings from which further features, embodiments and advantagesmay be taken, and in which:

FIGS. 1A to 1G illustrate cutting patterns of cellulose-containingarticles according to the present invention. Particularly, FIGS. 1A and1B show the cutting pattern of an inventive cellulose-containingarticles adapted to be applied on the face (face mask); FIG. 1C showsthe cutting pattern of an inventive cellulose-containing article adaptedto be applied on or around the mouth (mouth mask); FIG. 1D shows thecutting pattern of an inventive cellulose-containing article adapted tobe applied on the forehead (forehead mask); FIG. 1E shows the cuttingpattern of an inventive cellulose-containing article in the form of a 10cm×10 cm overlay; FIG. 1F shows the cutting pattern of an inventivecellulose-containing article adapted to be applied on the eyes (eyemask); and FIG. 1G shows the cutting pattern of an inventivecellulose-containing article adapted to be applied on single eyes (eyepads).

The face mask as shown in FIGS. 1A and 1B may particularly be providedwith an average thickness of about 2 mm or with an average thickness ofabout 0.8 to 1 mm. The face mask may have a width of 185 mm and a heightof 175 mm. Alternatively, the face mask may be provided with a width of240 mm and a height of 175 mm.

The mouth mask as shown in FIG. 1C may particularly be provided with anaverage thickness of about 1 mm. Alternatively the mouth mask may beprovided with an average thickness of about 2 mm. The mouth mask mayhave a width of 125 mm and a height of 85 mm.

The forehead mask as shown in FIG. 1D may particularly be provided withan average thickness of about 1 mm. Alternatively the forehead mask maybe provided with an average thickness of about 2 mm. The forehead maskmay have a width of 190 mm and a height of 60 mm.

The overlay as shown in FIG. 1E may particularly be provided with anaverage thickness of about 2 mm. Alternatively the overlay may beprovided with an average thickness of about 0.8 to 1 mm. The overlay mayhave a width of 100 mm and a height of 100 mm.

The eye mask as shown in FIG. 1F may particularly be provided with anaverage thickness of about 2 mm. Alternatively the eye mask may beprovided with an average thickness of about 1 mm. The eye mask may havea width of 191 mm and a height of 60 mm.

The eye pads as shown in FIG. 1G may particularly be provided with anaverage thickness of about 1.0 to 2.0 mm. The eye pads may have each awidth of 75 mm and a height of 35 mm.

FIG. 2 shows the CP/MAS 13C-spectra of cellulose of the strain ATCC11142 (upper panel) and of the strain DSM 14666 (middle panel)manufactured using a continuous semi-static cellulose manufacturingprocess in comparison to the comparative example (lower panel).

DETAILED DESCRIPTION OF THE INVENTION EXAMPLE 1

The cellulose-containing article according to the present invention andmanufactured using a semi-static continuous process was compared withregard to its material characteristics to a cellulose-containing articlemanufactured using a static and discontinuous culture (comparativeexample).

Molecular Structure

The molecular structure of the article according to the presentinvention was determined using gel permeation chromatography (GPC).

For this purpose cellulose of the strain ATCC 11142 was used. Thecomparative example was produced using a static cellulose manufacturingprocess. The article according to the present invention was producedusing a continuous semi-static cellulose manufacturing process.

The GPC-measurement was performed using 0.9% (m/v) LiCl/DMAc-solutionaccording to Röder et al (RÖDER T, MORGENSTERN B, SCHELOSKY N, GATTER O:Solutions of cellulose in N,N-dimethylacetamide/LiCl by light scatteringmethods. Polymer (2001), 42/16, 6765-73.) with dissolved dry-frozen BCsamples and was performed using four serial GPC-columns (PL Gel ALS, 20μm, 7.5×300 mm) and using three detectors (Fluorescence, MALLS andRefraction index). An 0.9% (m/v) LiCl/DMAc-solution was used as theeluent. Filtration was performed using an 0.02 μm-filter. The flow ratewas 1 ml/min, the injection volume was 100 μl and the running time was45 min. For labeling of the carbonyl groups a fluorescence marker wasused and measured fluorometrically. For evaluation the programCS53_76-79 according to Röhrling et al. (RÖHRLING J, POI I HAST A,ROSENAU T, LANGE T, EBNER G, SIXTA H, KOS-MA P A: Novel method for thedetermination of carbonyl groups in cellulosics by fluorescencelabelling. 1. Method development. Biomacromolecules (2002), 3, 959-68)was used.

Table 1 shows the results. Particularly, the molecular characteristicsare shown in table 1 of an article according to batches of articlesaccording to the present invention (sample 1 and sample 2), and onecomparative example.

TABLE 1 Car- Carbon- bonyl- ylend- Mn DP_(n) M_(w) PDI groups groups[g/mol] [M_(n)/M₀] [g/mol] [M_(w)/M_(n)] [μmol/g] [μmol/g] compar-308300 1902 1069000 3.5 8.50 3.24 ative example sample 1 305200 1882 775800 2.5 5.61 3.28 sample 2 355900 2195  627100 1.8 3.46 2.80

Thereby, the amount of carbonyl-end-groups was determined based on DPn.

The present inventors have surprisingly found that the length of thecellulose chains of samples 1 and 2, manufactured using a continuoussemi-static process are more uniform than the cellulose chains of thecomparative example, manufactured with a static culturing. This isparticularly reflected by the relatively low PDI-value of sample 1 andsample 2. The comparative example, however, comprises a mixture of long-and short chains of cellulose. This also explains the differences shownbetween the theoretical and the experimentally determined value of theamounts of carbonyl groups

Near Structure

The near structure of the article according to the present invention wasdetermined using NMR.

For this purpose cellulose of the strain ATCC 11142 and of the strainDSM 14666 was used. The comparative example was produced as a wet fleeceusing a static cellulose manufacturing process. The article according tothe present invention was produced as a wet fleece using a continuoussemi-static cellulose manufacturing process.

For determination of cellulose lα and lβ as well as the crystallinity ofnever-dried BC-samples solid-state-13C-NMR-spectroscopy was performed.The 13C-CP-MAS having a TPPM decoupling (4 mm High-Kopf) was performedusing a 400 MHz-Avance II-Spectrometer of Bruker, at a static magneticfield of 9,4 T. The rotational frequency in the measurement of thesample was 5 kHz and the relaxation time (the time between the scans)was 2 seconds.

FIG. 2 shows the CP/MAS 13C-spectra of cellulose of the strain ATCC11142 (upper panel) and of the strain DSM 14666 (middle panel)manufactured using a continuous semi-static cellulose manufacturingprocess in comparison to the comparative example (lower panel). It isimmediately apparent therefrom that also in the CP/MAS 13C-spectra thesamples from the continuous semi-static manufacturing method differ inthe samples from the static manufacturing method. Table 2 below showsthe content of cellulose lα and lβ, respectively, and the crystallinityIc based on the CP/MAS 13C NMR.

The results of the NMR experiment confirm the results achieved by theabove-described GPC-analysis.

TABLE 2 strain Iα [%] Iβ [%] Iα/Iβ Ic [%] DSM comp. example 43 20 2, 286 14666 inventive sample 40 17 2, 4 86 ATCC comp. example 35 15 2, 2 8111142 inventive sample 34 14 2, 4 82

Supra Molecular Structure

The supra molecular structure was determined using REM in 2,000-foldmagnification after labeling with leading carbon and subsequent goldsputtering. Electron-microscope Leica S440i, with tungsten cathode tomaximum of 30kV, scintillation-SE-detector, 4-quadrantfieldsemi-conductor RE-detector. The respective BNC fleeces of cellulose ofthe strain ATCC 11142 and of the strain DSM 14666 were freeze-dried andsubsequently subjected to REM. It was found that independent of theutilized strain the supra molecular structure of the inventive samples(continuous semi-static cellulose manufacturing process) wasindistinguishable from the supra molecular structure of the comparativesamples (static cellulose manufacturing process).

Surface Structure

The surface structure of cellulose-containing articles is of importance,particularly if applied as wound dressing or cosmetic product. Thesurface structure was analyzed using laser scanning microscopy-(LSM).For this purpose BNC-fleeces of strains ATCC 11142 and DSM 14666,respectively, were produced in a static process and in a semi-staticcontinuous process, respectively.

Hot pressing of the samples was performed at 120° C. for 10 min (d≤50μm) or 20 min (d≥50 μm) using Yellow Press 4050/Schulze Thermal TransferPress.

LSM-pictures of the upper surfaces and the lower surfaces of wet fleecesof the bacterial strain ATCC 11142 produced in a semi-static continuousprocess and in a static process revealed that the surface structure offleeces produced in a semi-static continuous process wasindistinguishable of the surface structure of fleeces produced in astatic process.

Water Absorption Capacity, Water Retention Capacity and Tensile Strength

BNC by nature forms a hydro gel, which results in its characteristicliquid affinity of water or other organic solutions. Thereby, the waterabsorption capacity and the water retention capacity of the BNC-articlesare important features.

After purification of the BNC-samples and consecutive washing stepsusing a.dest until the washing water was neutral (determined withunitestpaper), the average weight of the never-dried samples wasdetermined.

The WRC was determined using standardized conditions as described inJayme & Rothamel (JAYME G, ROTHAMEL L: Composition of the extractivesobtained from black poplarwood and of those found in the resultingsulfite and sulfate pulps. Cellulose-Chemie (1944), 22, 88-96). Thesamples to be determined were cut into pieces of 0.5 cm2. Thenever-dried BNC-samples were centrifuged for 15 min, at 4000 U/min (rpm)and the wet weight was determined. 4000 rpm correspond to about 1788 g.After air drying at 100° C. in a drying chamber to constant weight, theWRC was determined using the quotation

WRC=(mass wet−mass dry)/mass wet×100%

The re-quelling of the dried samples was performed at 30° C. for 2 hrs.in a.dest.

Table 3 shows the water absorption capacity (WAC) and the waterretention capacity (WRC) of wet BNC fleeces of the respective bacterialstrain manufactured in a semi-static continuous process and in a staticprocess, respectively.

TABLE 3 Strain manufacturing method WAC [%] WRC [%] DSM 14666 static 16900 ± 1.520 853 ± 94 DSM 14666 semi-static, continuous 14.000 ± 1.260900 ± 99 ATCC 11142 static 13.195 ± 1.310 815 ± 85 ATCC 11142semi-static, continuous 11.003 ± 1.083 781 ± 83

Furthermore the tensile strength was determined. The tensile strength isa preferable measure for the uniformity of the BNC. The BNC fleeces werehot pressed. The BNC fleeces manufactured in a semi-static continuousprocess revealed a higher tensile strength compared with the BNC fleecesmanufactured in a static process. BNC fleeces manufactured in a staticprocess showed a tensile strength of 252 MPa, whereas BNC fleecesmanufactured in a semi-static continuous process showed a bendingtensile strength of 312 MPa.

The features of the present invention disclosed in the specification,the claims, examples and/or the figures may both separately and in anycombination thereof be material for realizing the invention in variousforms thereof.

What is claimed is:
 1. A method of manufacturing an article containingbiotechnologically produced nanostructured cellulose (BNC), comprising:providing a BNC non-woven in a continuous semi-static process, includingproducing BNC from a bacterial culture in a cultivation medium, andproviding the article, the article comprising BNC of microbial origin inan amount of at least 1% by weight and at most 15% by weight; and fluidin an amount of at least 85% by weight and at most 99% by weight.
 2. Themethod according to claim 1, wherein the fluid comprises water.
 3. Themethod according to claim 1, comprising the step of: adding cultivationmedium and/or constituents of the cultivation medium during bacterialculture.
 4. The method according to claim 1, comprising the step of:harvesting or removing BNC non-woven from the bacterial culture duringBNC synthesis.
 5. The method according to claim 4, wherein harvesting orremoving BNC non-woven is done stepwise or continuously.
 6. The methodaccording to claim 1, wherein providing the BNC non-woven comprises,providing a reaction vessel comprising cultivation medium; inoculatingthe cultivation medium with a BNC-producing bacterial strain; andbacterial synthesis of BNC in the reaction vessel.
 7. The methodaccording to claim 1, wherein a cell count is from 10⁴ to 10⁷ cells/mlof cultivation medium during the culture.
 8. The method according toclaim 1, wherein the cultivation medium comprises a carbon source, anitrogen source and/or a vitamin source.
 9. The method according toclaim 1, wherein the cultivation medium comprises a buffer.
 10. Themethod according to claim 8, wherein the cultivation medium comprisesthe carbon source in an amount of at least 10 g/l.
 11. The methodaccording to claim 8, wherein the cultivation medium comprises thenitrogen source in an amount of at least 2 g/l.
 12. The method accordingto claim 8, wherein the cultivation medium comprises the vitamin sourcein an amount of at least 2 g/l.
 13. The method according to claim 1,wherein a cultivation temperature is at least 20° C. and/or at most 36°C.
 14. The method according to claim 1, wherein a cultivation time is atleast 1 day.
 15. The method according to claim 1, wherein a culturevolume is at least 10,000 ml.
 16. The method according to claim 1,wherein a synthesis area is at least 10 m².
 17. The method according toclaim 1, wherein a weight average molecular weight of the BNC is at most1,000,000 g/mol.
 18. The method according to claim 1, wherein providingthe article includes adapting the article's shape to an area of skin,including the face, a part of the face, the mouth, forehead, or theeyes.
 19. The method according to claim 1, wherein providing the articleincludes cutting the non-woven to the desired shape.
 20. The methodaccording to claim 19, wherein cutting is performed with a fluid jet.21. The method according to claim 20, wherein the fluid jet has adiameter of from 100 to 300 μm.
 22. The method according to claim 1,comprising sterilizing the article.
 23. The method according to claim22, wherein sterilizing is e-beam sterilization.